Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study.

BACKGROUND: Performing cognitive-motor dual tasks (DTs) may result in reduced walking speed and cognitive performance. The effect in persons with progressive multiple sclerosis (pwPMS) having cognitive dysfunction is unknown. OBJECTIVE: To profile DT-performance during walking in cognitively impaired pwPMS and examine DT-performance by disability level. METHODS: Secondary analyses were conducted on baseline data from the CogEx-study. Participants, enrolled with Symbol Digit Modalities Test 1.282 standard deviations below normative value, performed a cognitive single task ([ST], alternating alphabet), motor ST (walking) and DT (both). Outcomes were number of correct answers on the alternating alphabet task, walking speed, and DT-cost (DTC: decline in performance relative to the ST). Outcomes were compared between EDSS subgroups (≤ 4, 4.5-5.5, ≥ 6). Spearman correlations were conducted between the DTCmotor with clinical measures. Adjusted significance level was 0.01. RESULTS: Overall, participants (n = 307) walked slower and had fewer correct answers on the DT versus ST (both p < 0.001), with a DTCmotor of 15.8% and DTCcognitive of 2.7%. All three subgroups walked slower during the DT versus ST, with DTCmotor different from zero (p's < 0.001). Only the EDSS ≥ 6 group had fewer correct answers on the DT versus ST (p < 0.001), but the DTCcognitive did not differ from zero for any of the groups (p ≥ 0.039). CONCLUSION: Dual tasking substantially affects walking performance in cognitively impaired pwPMS, to a similar degree for EDSS subgroups.

NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study.

BACKGROUND AND PURPOSE: The secondary progressive phase of multiple sclerosis is characterised by disability progression due to processes that lead to neurodegeneration. Surrogate markers such as those derived from MRI are beneficial in understanding the pathophysiology that drives disease progression and its relationship to clinical disability. We undertook a 1H-MRS imaging study in a large secondary progressive MS (SPMS) cohort, to examine whether metabolic markers of brain injury are associated with measures of disability, both physical and cognitive. MATERIALS AND METHODS: A cross-sectional analysis of individuals with secondary-progressive MS was performed in 119 participants. They underwent 1H-MR spectroscopy to obtain estimated concentrations and ratios to total Cr for total NAA, mIns, Glx, and total Cho in normal-appearing WM and GM. Clinical outcome measures chosen were the following: Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Nine-Hole Peg Test, Timed 25-foot Walk Test, and the Expanded Disability Status Scale. The relationship between these neurometabolites and clinical disability measures was initially examined using Spearman rank correlations. Significant associations were then further analyzed in multiple regression models adjusting for age, sex, disease duration, T2 lesion load, normalized brain volume, and occurrence of relapses in 2 years preceding study entry. RESULTS: Significant associations, which were then confirmed by multiple linear regression, were found in normal-appearing WM for total NAA (tNAA)/total Cr (tCr) and the Nine-Hole Peg Test (ρ = 0.23; 95% CI, 0.06-0.40); tNAA and tNAA/tCr and the Paced Auditory Serial Addition Test (ρ = 0.21; 95% CI, 0.03-0.38) (ρ = 0.19; 95% CI, 0.01-0.36); mIns/tCr and the Paced Auditory Serial Addition Test, (ρ = -0.23; 95% CI, -0.39 to -0.05); and in GM for tCho and the Paced Auditory Serial Addition Test (ρ = -0.24; 95% CI, -0.40 to -0.06). No other GM or normal-appearing WM relationships were found with any metabolite, with associations found during initial correlation testing losing significance after multiple linear regression analysis. CONCLUSIONS: This study suggests that metabolic markers of neuroaxonal integrity and astrogliosis in normal-appearing WM and membrane turnover in GM may act as markers of disability in secondary-progressive MS.

Patient perspective on decisions to switch disease-modifying treatments in relapsing-remitting multiple sclerosis.

BACKGROUND: There are now large cohorts of people with relapsing-remitting multiple sclerosis (pwRRMS) who have taken several Disease-Modifying Treatments (DMTs). Studies about switching DMTs mostly focus on clinical outcomes rather than patients' decision-making. Neurologists are now required to support decisions at various times during the relapsing disease course and they do so with concerns about DMTs risks. This qualitative study investigates how pwRRMS weigh up the pros and cons of DMTs, focusing on perceptions of effectiveness and risks when new treatments are considered. OBJECTIVE: To increase understanding of people's experiences of decision-making when switching DMTs. METHODS: 30 semi-structured interviews were conducted with pwRRMS in England. 16 participants had switched DMT and their experiences were compared with those who had only taken one DMT. Interviews were analysed thematically to answer: what main factors influence people's decision-making to switch DMTs and why? RESULTS: Of the 16 participants with experience of switching DMT, eight had taken two or more DMTs; eight had taken three or more. Two was the DMT median. This study demonstrated that despite the term "switching" implying that similar treatments are inter-changeable, for pwRRMS taking new treatments involves different emotions, routines, risks, prognosis and communication experiences. Two meta themes identified were: 1) A distinctive, rapid and emotional decision-making process where old emotions related to MS prognosis are revisited. 2) Switching has a different impact on communication for escalation or de-escalation processes. CONCLUSION: Switching DMT involves different routines, risks, prognosis and communication experiences. These decisions are emotionally difficult because of the fear about transitioning to secondary progressive MS, and DMT effectiveness uncertainty. Patient centred decision aids should include information about first and consecutive treatment decisions.

Identifying barriers to help-seeking for sexual dysfunction in multiple sclerosis.

BACKGROUND: Sexual dysfunction (SD) is common in multiple sclerosis (MS), however, under-reported. OBJECTIVE: The aim of this study was to identify barriers faced by patients with MS and healthcare professionals (HCPs) in discussing SD. METHODS: This was a two-part prospective study carried out at a tertiary care centre. Patients with MS were surveyed using a 29-item questionnaire and SD was assessed using the MSISQ and ASEX questionnaires; depression screened with PHQ-2. HCPs were surveyed using a 23-item questionnaire. RESULTS: Seventy four patients (mean age 42.4 ± 10.7, 54 females) and 98 HCPs (mean age 45.8 ± 8.9, 90 females) participated. SD was significant, with primary (36.4%), secondary (27%) and tertiary (29.8%) contributory factors. Commonest barriers reported by patients were dominance of neurological symptoms (N = 30, 40.5%), presence of family or friends (N = 28, 37.8%), and not being asked (N = 25, 33.8%), while HCPs reported presence of family or friends (N = 34, 34.7%), lack of knowledge about SD (N = 30, 30.6%), and inadequate time during the consultation (N = 27, 27.6%). CONCLUSIONS: Barriers to discussing SD are similar between patients and HCPs. The most common barriers are addressable through modifications in the clinic environment, raising awareness and providing training opportunities.

2017 McDonald diagnostic criteria: A review of the evidence.

The diagnosis of Multiple Sclerosis (MS) has continuously evolved, allowing for an earlier and more accurate diagnosis of MS over time. The McDonald Criteria for diagnosis of MS were originally proposed in 2001, with previous revisions in both 2005 and 2010. The International Panel on Diagnosis in MS have recently reviewed the 2010 McDonald Criteria, and made recommendations for the revised 2017 McDonald Criteria. Any revisions made relied entirely on the available evidence, and not expert opinion. In this review, we provide an overview of the recent 2017 revisions to the McDonald Criteria, focusing in particular on the motivating evidence behind the recommendations made. We also review the existing research around misdiagnosis in MS, as well as areas considered to be high priorities of research, currently lacking in sufficient evidence, which may influence future diagnostic criteria in years to come. Finally, we illustrate some clinical examples, to demonstrate the impact of new diagnostic criteria on time to MS diagnosis in a real-world setting.

Validating the portal population of the United Kingdom Multiple Sclerosis Register.

The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

Negotiating the radiologically isolated syndrome.

Multiple sclerosis, always challenging, hands down a particular gauntlet with the concept of the radiologically isolated syndrome. This article discusses what it is, recent developments in the field and how these patients should be managed.

Testing for urinary tract colonization before high-dose corticosteroid treatment in acute multiple sclerosis relapses: prospective algorithm validation.

BACKGROUND AND PURPOSE: To evaluate a dipstick algorithm for urinary tract colonization, prior to high-dose corticosteroid treatment in acute relapses of multiple sclerosis (MS). METHODS: Prospective cohort study of 267 consecutive patients with MS relapses requiring corticosteroid treatment in a hospital-based, ambulatory, acute MS relapse clinic. A total of 18 participants met the exclusion criteria, leaving 249 for analysis. Main outcome measures were urinary dipstick sensitivity, specificity, positive predictive value, negative predictive value and safety of antibiotic co-treatment with high-dose corticosteroids. RESULTS: Significant bacteriuria (≥10(5) colonies ml) rate in this population was 11% (95% CI, 7.1-14.9). Specificity and sensitivity of positive leucocyte esterase or nitrite were 78% and 65%. Negative predictive value of urine dipstick was 96%. No clinical adverse events occurred in the 3% (95% CI, 0.9-5.1) of patients with a false-negative dipstick. Eighteen per cent of patients were unnecessarily treated with antibiotics for 48 h. CONCLUSION: Urinary dipstick testing allows for rapid and safe management of patients suffering from an acute MS relapse. The algorithm is conservative, and future work is needed to reduce the false-positive rate.

It is better to be in a clinical trial than not: lessons learnt from clinical neurology--the management of acute multiple sclerosis relapses.

OBJECTIVE: To compare being on-, or off-, a randomized controlled trial (RCT) for the same intervention. DESIGN: Cohort study. SETTING: Ambulatory outpatient clinic in a clinical neurosciences centre. SUBJECTS: Patients experiencing a clinically significant multiple sclerosis (MS) relapse, who received a 3-day regimen of intravenous methylprednisolone as an ambulatory outpatient, were compared with a similar group of patients who had previously been treated exactly in the same way while participating in a RCT. MAIN OUTCOME MEASURES: The Multiple Sclerosis Relapse Management Scale (MSRMS) was used to measure patients' experiences of relapse management in both groups. The two groups were compared under four main headings: interpersonal care, access to care, information and coordination of care. RESULTS: The principal finding was that interpersonal care was significantly worse in the off-trial group (P = 0.0001), implying a beneficial trial effect on patient experience. CONCLUSION: The effect observed is likely secondary to trial participation; both groups had similar baseline features, and were treated in the same way. Likely mechanisms for the differences are protocol, care and Hawthorne effects. The findings support the incorporation of structured RCT-style practice into routine clinical management, in order to deliver a more patient-centred care in the treatment of MS relapses. This may have implications for other chronic neurological diseases.

Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine.

Sodium blockade with lamotrigine is neuroprotective in animal models of central nervous system demyelination. This study evaluated the effect of lamotrigine on magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure of intact brain tissue, in a group of subjects with secondary progressive multiple sclerosis (MS). In addition, the utility of MTR measures for detecting change in clinically relevant pathology was evaluated. One hundred seventeen people attending the National Hospital for Neurology and Neurosurgery or the Royal Free Hospital, London, UK, were recruited into a double-blind, parallel-group trial. Subjects were randomly assigned by minimisation to receive lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating and assessing physicians and patients were masked to treatment allocation. Results of the primary endpoint, central cerebral volume, have been published elsewhere. Significant differences between the verum and placebo arms were seen in only two measures [normal appearing grey matter (NAGM) p = 0.036 and lesion peak height (PH) p = 0.004], and in both cases there was a greater reduction in MTR in the verum arm. Significant correlations were found of change in MS functional composite with all MTR measures except lesion and normal appearing white matter (NAWM) PH. However, the change in MTR measures over 2 years were small, with only NAGM mean (p = 0.001), lesion peak location (p = 0.11) and mean (p < 0.0001) changing significantly from baseline. These data did not show that lamotrigine was neuroprotective. The clinical correlation of MTR measures was consistent, but the responsiveness to change was limited.

Clinical and imaging correlates of the multiple sclerosis impact scale in secondary progressive multiple sclerosis.

The association of pathology and neurological deficit with quality of life (QoL) in multiple sclerosis (MS) is not fully understood. In this study, magnetic resonance imaging (MRI) measures of pathology--T1 and T2 lesion volume and ratio; active T2 lesion number; global and regional brain volume and atrophy; magnetization transfer ratio (MTR) for lesions, normal appearing grey and white matter (NAGM, NAWM); and spinal cord cross-sectional area-and measures of neurological disability (expanded disability status scale, EDSS), deficit (MS functional composite, MSFC) and inflammatory activity (relapse rate) were compared with the MS impact scale (MSIS-29), in participants in a trial of lamotrigine in secondary progressive MS. Data were collected from 118 people (85 female:33 male) aged 30-61 years (mean 50.6 years)--median EDSS 6.0 (range 4.0-7.5); mean disease duration 20.1 years (range 3-41)--at baseline and 2 years. Regression analysis was used to identify independently significant cross-sectional and longitudinal correlates of the physical (MSIS-phys) and psychological (MSIS-psych) components of the MSIS-29; longitudinal analysis using the 57 people in the placebo arm. The only independently significant correlate of MSIS-phys was 1/timed walk (TW) (p < 0.0001, R (2) = 0.13; p = 0.047, R (2) = 0.09); cross-sectionally the best model for MSIS-psych was the paced auditory serial addition test (PASAT-3) (p = 0.041) and T1-to-T2 lesion volume ratio (p = 0.009) (R (2) = 0.13); longitudinally it was change in 1/TW (p = 0.007), mean NAWM MTR (p = 0.003) and NAGM peak height (p = 0.048) (R (2) = 0.32). These data show that MRI measures and clinical measures do impact on quality of life, but the association is limited.

Designing a seamless phase II/III clinical trial using early outcomes for treatment selection: an application in multiple sclerosis.

In recent years adaptive seamless phase II/III designs (ASDs) allowing treatment or dose selection at an interim analysis have gained much attention because of their potential to save development costs and to shorten time-to-market of a new compound compared to conventional drug development programmes with separate trials for individual phases. In this paper, we describe an ASD with treatment selection based on early outcome data, specifically considering the situation where no final outcomes are observed at the time of the interim analysis. Bringing together combination tests for adaptive designs and the closure principle for multiple testing, control of the familywise type I error rate in the strong sense is achieved. Furthermore, a simulation model is proposed based on standardized test statistics that allows the generation of virtual trials for a variety of outcomes. We use this simulation model to investigate the actual type I error rate of the proposed testing procedure and find that the familywise type I error rate is controlled as expected. The method is often conservative, with the degree of conservatism depending on the correlation between early and late outcome, the true mean values of the early outcome in the different treatment groups and the selection rule. The investigations are motivated and illustrated by an application of the proposed design and simulation model to progressive multiple sclerosis.

A longitudinal study of MRI-detected atrophy in secondary progressive multiple sclerosis.

MRI measures of tissue atrophy within the central nervous system may reflect the neurodegenerative process which underpins the progressive phase of multiple sclerosis (MS). There has been limited longitudinal investigation of MRI-detected atrophy in secondary progressive MS. This study includes 56 subjects with secondary progressive MS. Subjects were followed up for 2 years and MRI analysis was conducted at 12 month intervals using the following measures: (1) whole brain (WB) volume change; (2) grey and white matter (WM) volumes; (3) central brain volume; (4) upper cervical spinal cord (SC) area; (5) T2 lesion volumes. Clinical measures included the Expanded Disability Status Scale and the MS Functional Composite. All volumetric MRI measures were assessed for sensitivity, responsiveness, reliability and correlation with disability. The mean annual atrophy rate of WB was 0.59% per year and this was the most responsive atrophy measure assessed. Grey matter (GM) atrophy (-1.18% per year) was greater and more responsive than WM atrophy (0.12% per year). The SC demonstrated the highest atrophy rate at 1.63% per year. WB, GM and SC atrophy all correlated with change in the Multiple Sclerosis Functional Composite z score (r = 0.35, 0.42, 0.34), and GM atrophy was the only correlate of change in the 9 Hole Peg Test and Paced Auditory Serial Addition Test performance. None of the MRI measures correlated with Expanded Disability Status Score progression. Measures of WB, GM and SC atrophy all have attributes for use as surrogate markers in secondary progressive MS trials and improvement in the reliability of the GM and SC volume measurements may enhance these further.

South Asian strokes: lessons from the St Mary's stroke database.

BACKGROUND: South Asians comprise the largest ethnic minority population in the UK. This subgroup is known to have an elevated risk of stroke. However, there is limited data on patterns of cerebrovascular disease and associated risk factors in this population. AIM: The aim of this study was to analyse differences in stroke subtype and risk factor profile between South Asian and White stroke patients admitted to a central London teaching hospital. DESIGN: Prospective database of all admissions to the St Mary's Hospital stroke unit. METHODS: We examined ethnicity, stroke subtype and risk factor profile of consecutive patients admitted to the stroke unit between 8 October 2003 and 14 February 2007. RESULTS: A total of 811 patients were identified of whom 736 had strokes. Four hundred and ninety-six (67%) occurred in the White subgroup, and 72 (10%) in the Asian subgroup. The South Asian subgroup was significantly younger (65 vs. 73 years in the White subgroup; P < 0.001). They had higher rates of hypertension (age adjusted frequency 87% vs. 64%; P < 0.0001), diabetes (54% vs. 15%; P < 0.0001), and hyperlipidaemia (70% vs. 45%; P = 0.001). There were lower rates of smoking (15% vs. 33%; P < 0.0001).There was a trend towards more lacunar infarcts and less total anterior circulation infarcts in South Asians, although after age adjustment this was not significant at the 5% level. CONCLUSION: The South Asian subgroup has shown important differences in risk factor profile compared with the White population. The higher frequency of hypertension, diabetes and hyperlipidaemia seen in this subgroup are an important consideration in designing secondary prevention programmes tailored specifically to this community.

Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis.

BACKGROUND: Although MRI measures of grey matter abnormality correlate with clinical disability in multiple sclerosis, it is uncertain whether grey matter abnormality measured on MRI is entirely due to a primary grey matter process or whether it is partly related to disease in the white matter. METHODS: To explore potential mechanisms of grey matter damage we assessed the relationship of white matter T2 lesion volume, T1 lesion volume, and mean lesion magnetisation transfer ratio (MTR), with MRI measures of tissue atrophy and MTR in the grey matter in 117 subjects with secondary progressive multiple sclerosis. RESULTS: Grey matter fraction and mean grey matter MTR were strongly associated with lesion volumes and lesion MTR mean (r = +/-0.63-0.72). In contrast, only weak to moderate correlations existed between white matter and lesion measures. In a stepwise regression model, T1 lesion volume was the only independent lesion correlate of grey matter fraction and accounted for 52% of the variance. Lesion MTR mean and T2 lesion volume were independent correlates of mean grey matter MTR, accounting for 57% of the variance. CONCLUSIONS: Axonal transection within lesions with secondary degeneration into the grey matter may explain the relationship between T1 lesions and grey matter fraction. A parallel accumulation of demyelinating lesions in white and grey matter may contribute to the association of T2 lesion volume and lesion MTR with grey matter MTR.

Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis.

Although there is substantial brain grey matter pathology in secondary progressive multiple sclerosis (MS), there has been limited investigation of its contribution to disability.This study investigated the correlation of magnetization transfer ratio (MTR) measures taken from brain grey matter, normal appearing white matter (NAWM) and lesions with neurological deficit and disability in 113 people with secondary progressive MS. In order to adjust for the potential effects of focal white matter lesions and global brain atrophy, T2 lesion volume and normalized brain volume (NBV) were also calculated for each subject. Clinical measures included the expanded disability status scale (EDSS) and the multiple sclerosis functional composite (MSFC) scores. Linear regression analysis was used to assess the age- and gender-adjusted correlation of MTR histogram mean, peak height and peak location with the MSFC and individual component measures. Logistic regression analysis was used to determine whether imaging measures could be used to predict if subjects were in the higher disability group (EDSS > or = 6.5).Significant correlations were detected between MSFC composite and mean MTR in (i) normal appearing white matter (NAWM; r = 0.327, p < 0.0001), (ii) grey matter (r = 0.460, p < 0.0001) and (iii) lesions (r = 0.394, p < 0.0001). Although NBV and T2 lesion volume correlated significantly with MSFC, grey matter histogram mean emerged as the best predictor of MSFC score. None of the MRI measures significantly predicted higher EDSS.These results suggest that brain grey matter pathology plays an important role in determining neurological impairment. The apparent paucity of correlation between MRI measures and EDSS is likely to represent the relative insensitivity of the latter measure in this study group.

FAST-TIA: a prospective evaluation of a nurse-led anterior circulation TIA clinic.

BACKGROUND: Transient ischaemic attacks (TIAs) carry a significant early risk of stroke. New national guidelines state patients should be seen within 7 days of the incident, with higher-risk patients being seen within 24 h. Meeting these targets across the NHS poses a significant challenge. A novel approach to TIA assessment has been developed using a nurse-led rapid-access anterior circulation TIA clinic. METHODS: This was a prospective evaluation of all patients attending the FAST-TIA clinic between November 2003 and December 2006. Diagnostic yield of neurovascular events among patients seen through the TIA service and median time from referral to assessment and from event to assessment were measured. RESULTS: 282 patients were eligible for investigation, and seen through the clinic over a period of 38 months. A vascular event was diagnosed in 242 (86%). TIA was diagnosed in 133 (55%), minor ischaemic stroke in 77 (32%), haemorrhagic stroke in three (1%), and an ocular event in 29 (12%). Median time from referral to assessment was 3 days (interquartile range (IQR) 1-7), and from event to assessment it was 7 days (IQR 3-18). 34% of patients were seen within 24 h of referral. CONCLUSIONS: This model has a high diagnostic rate of 86% vascular events, significantly higher than current national averages of approximately 55%. Current national guidelines for early assessment of patients (published subsequent to this study) are achievable using this service. The FAST-TIA model is an easily reproducible and pragmatic method of improving the diagnostic yield of TIA services, while keeping within national targets.

Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis.

BACKGROUND: Neuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation. METHODS: Clinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC). RESULTS: All MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure. CONCLUSIONS: This data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS.

Global health public-private partnerships: IAVI, partnerships and capacity building.

New developments in biotechnology and the need to overcome the lack of incentive for investment in vaccines for diseases affecting Africa have led to the promotion of product development public-private partnerships (PPP). Our work at the ESRC INNOGEN Research Centre assesses the way in which these collaborative mechanisms approach their mission of getting science to work for the poor and what they contribute to broader development objectives, particularly in relation to capacity building. Case study research of the International AIDS Vaccine initiative (IAVI) and their work on the ground in Africa and India has highlighted two legal related issues. First, by working as a PPP the organisation has changed the 'ownership' of science, making the process more flexible and emphasising a bottom-up dialogue process while advocating a private sector ethos. Second--whether intentionally or not--the partnership's emphasis on advocacy and communications has increased the importance of knowledge generation and management activities within the partnership and its availability to stakeholders. This paper attempts to ascertain the impact of these issues for the building of health research capacity.